Can EGCG Alleviate Symptoms of Down Syndrome by Altering Proteolytic Activity?

Down syndrome (DS), also known as "trisomy 21", is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. Silencing these extra genes is beyond existing technology and seems to be impractical. A number of pharmacologic options have been proposed to change the quality of life and lifespan of individuals with DS. It was reported that treatment with epigallocatechin gallate (EGCG) improves cognitive performance in animal models and in humans, suggesting that EGCG may alleviate symptoms of DS. Traditionally, EGCG has been associated with the ability to reduce dual specificity tyrosine phosphorylation regulated kinase 1A activity, which is overexpressed in trisomy 21. Based on the data available in the literature, we propose an additional way in which EGCG might affect trisomy 21-namely by modifying the proteolytic activity of the enzymes involved. It is known that, in Down syndrome, the nerve growth factor (NGF) metabolic pathway is altered: first by downregulating tissue plasminogen activator (tPA) that activates plasminogen to plasmin, an enzyme converting proNGF to mature NGF; secondly, overexpression of metalloproteinase 9 (MMP-9) further degrades NGF, lowering the amount of mature NGF. EGCG inhibits MMP-9, thus protecting NGF. Urokinase (uPA) and tPA are activators of plasminogen, and uPA is inhibited by EGCG, but regardless of their structural similarity tPA is not inhibited. In this review, we describe mechanisms of proteolytic enzymes (MMP-9 and plasminogen activation system), their role in Down syndrome, their inhibition by EGCG, possible degradation of this polyphenol and the ability of EGCG and its degradation products to cross the blood-brain barrier. We conclude that known data accumulated so far provide promising evidence of MMP-9 inhibition by EGCG in the brain, which could slow down the abnormal degradation of NGF.

The electrical activity of the masticatory muscles in children with cleft lip and palate.

BACKGROUND: Information regarding masticatory muscle function in children with cleft lip and palate (CLP) is limited. As a consequence, research on masticatory muscle activity in cleft subjects is needed. AIM: To assess masticatory muscle activity in children surgically treated for CLP as well as identify the possible factors associated with this activity. DESIGN: The sample comprised 82 children with mixed dentition and Class I occlusions (25 children with unilateral CLP and 57 subjects with no cleft abnormalities). A DAB-Bluetooth Instrument (Zebris Medical GmbH, Germany) was used to take electromyographical (EMG) recordings of the temporal and masseter muscles both in the mandibular rest position and during maximum voluntary contraction (MVC). RESULTS: Patients with clefts showed a significant increase in temporal muscle activity at rest compared with the controls. The presence of clefts and unilateral posterior crossbites are factors strongly associated with increased temporal muscle EMG potentials during rest position. CONCLUSIONS: Children with clefts have altered temporal muscle function. The presence of posterior crossbites affects the temporal muscle activity in cleft subjects. Early diagnosis and orthodontic treatment of malocclusions are necessary to achieve functional improvement in these patients.

Craniofacial Morphology in Midline Cervical Cleft: Case Report and Review of Literature.

Congenital midline cervical cleft is a rare anomaly of the neck. This paper presents the case of a boy diagnosed with this disorder in which a preliminary orthodontic treatment was implemented. The craniofacial anomalies associated with this malformation produced a defect that could only be successfully treated through the implementation of orthodontic and surgical treatments. In this case, congenital midline cervical cleft was accompanied by certain disorders within the facial structures of the skull, primarily mandibular retrusion, flattening of the contour of the mandibular base, and a steep angle between the cranial base and the mandibular plane.

[Fixed appliance therapy in patients with impaired short-circuit in the anterior part of the maxilla]. / Terapia aparatem stalym u pacjentów z zaburzeniami zwarcia w przednim odcinku szczeki.

UNLABELLED: Malocclusion in the anterior segment of maxilla and mandible are easily visible not only for dentists but also for the doctors of other specialties. Early diagnosis and appropriate therapy is important not only for occlusion but also for aesthetic reasons. AIM: The aim of the paper is to evaluate the anterior segment of maxilla and mandible in patients with malocclusion in this part and correct occlusion in the lateral segments. MATERIALS AND METHODS: Medical documentation, i.e. medical history, extra- and intraoral radiograms, diagnostic casts, panoramic and lateral cephalometric radiograms of patients aged 7-12 diagnosed with malocclusion in the anterior segment of maxilla and mandible and who were treated with a fixed sectional appliance and facemask was analyzed. Descriptive and cephalometric features were analyzed before (T1) and after (T2) the treatment in 25 children. The differences between the status before and after the treatment, and the extent of change between T1 and T2 were analyzed. RESULTS: Statistical analysis of mean values of selected metrical features before (at T1) and after (at T2) the treatment has revealed that all metrical features concerning soft, bony and dental tissues determining the facial profile, the shape of the bony and dental structures have changed and have reached values which are closer to the norm for the population for selected features. The changes were statistically significant (p<0.0001). CONCLUSIONS: Treatment with fixed appliances segment facemask resulted in statistically significant improvement in the parameters investigated, which demonstrates the applicability of this therapy in the treatment of anterior maxillary segment in patients with mixed dentition.

Compound odontoma in the mandible--case study and literature review.

INTRODUCTION: Odontomas constitute a developmental defect of hard dental tissues and are classified as benign odontogenic tumours. They are composed of all dental structures and tissues: enamel, dentin, cementum and pulp. As regards histomorphological features, two types of odontomas have been differentiated: complex and compound. Odontomas represent from 4.7% to 76% of odontogenic tumours. Their aetiology has not been fully understood, yet injury, infection and genetic factors are often named among the causes. Odontomas are usually detected by chance in radiographic images taken in relation to disrupted eruption or mislocation of teeth. AIM OF STUDY: To present the case study of an erupting compound odontoma on the right side of the mandible in an 11-year-old girl. MATERIAL, METHODS AND RESULTS: The analysis covered medical documentation of the patient, diagnostic casts, orthopantomographs and cone beam computed tomography scans. The case study has been complemented with the review of up-to-date literature. A lesion composed of 30 odontoids was removed during one-day surgery without subsequent augmentation with bone substitute material. There were no post-surgery complications. A follow-up orthopantomograph taken 3 months later showed that the wound had been healing correctly, which made it possible to plan subsequent orthodontic treatment with a fixed appliance. CONCLUSIONS: 1. Odontomas are benign lesions which can be removed during one-day surgery without the absolute need of augmentation with xenogenic or allogenic material. 2. The pressure exerted by the plate of a removable appliance is very likely to initiate the eruption of the odontoma.

Malocclusions and craniofacial anomalies in a child with velo-cardio-facial syndrome.

Velo-Cardio-Facial syndrome (VCFS), also called 22q11.2 microdeletion syndrome, is a rare pathology. The syndrome is caused by 22q11.2 deletion, recognized as one of the most frequent pathogenic human microdeletions. The scope and severity of the phenotypic expression of 22q11.2 microdeletion is characterised by high variability, although cleft palate and congenital conotruncal malformations are among the clinical features often associated with that syndrome. In the presented case of a boy patient with submucous cleft palate and congenital cardiac defect, 22q11.2 microdeletion was identified at the age of 13 months. In the presented paper particular emphasis was placed on the issue of dental and orthodontic care in patients with changes in the oral cavity and the craniofacial area, as well as on the possibilities of treatment and prophylaxis. The necessity to perform a thorough examination of the oral cavity in infants was also underlined as a vital element of clinical assessment, in particular in the case of co-occurring structural defects of internal organs.

Long-term folow-up after distraction osteogenesis with face mask in cleft lip and palate patients - preliminary report.

INTRODUCTION: Patients with cleft lip and palate are often diagnosed with maxillary deficiency, i.e. the reduction of maxillary measurements in three dimensions. The method of distraction osteogenesis (DO) remedies the disorder caused by bone insufficiency by generating new bone tissue. Despite the fact that DO has long been considered an effective method to treat significant bone deficiencies, it is still not a standard treatment applied by clinicians to manage underdevelopment, especially in the maxillary area. There is only a small number of publications concerning the long-term follow-up results of the use of that method to treat patients with cleft lip and palate. THE OBJECTIVE: Long-term analysis of dentoskeletal changes in cleft lip and palate patients treated with distraction osteogenesis and the use of a facial mask. MATERIAL AND METHODS: In 2001-2004, 30 patients with cleft lip and palate and related maxillary deficiency were treated by means of distraction osteogenesis and a facial mask. However, due to incomplete documentation, only 15 persons, having full medical documentation and a set of cephalometric radiographs taken in three specified time periods, were qualified for the study. The cephalometric analysis was performed on the following lateral head radiographs: pre-distraction images (T0), images taken after active distraction (T1) and 5 years after the completion of the distraction process (T2). A group of 12 persons participated in the 5-year follow-up measurements (T2). RESULTS: Cephalometric assessment indicated that after the use of distraction osteogenesis, the maxilla advanced by the mean of 3.84 mm and the SNA angle increased by the mean of 2.76° (statistically significant data). The maxillary advancement was accompanied by downward mandibular rotation. Long-term assessment after 5 years indicated that the SNA angle was reduced by 0.64°. CONCLUSIONS: The use of distraction osteogenesis with a facial mask to manage maxillary deficiency deserves more attention. It requires a close cooperation of the orthodontic and surgical team, as well as high motivation on the part of the patient. In order to provide the final assessment of the long-term results, further studies need to be conducted on larger clinical material.

Comparison of bone and chronological age in different types of primary and secondary palate clefts.

BACKGROUND: The ability to correctly assess the patient's bone age is an important element that allows correct diagnosis and proper planning of the start of orthodontic treatment. OBJECTIVE: The objective of this study was to estimate bone age in children with congenital craniofacial defects - primary and secondary palate cleft. MATERIAL AND METHODS: The analysis covered lateral head images of 45 patients 8 to 15 years old with different types of cleft (primary and secondary palate cleft, bilateral, right or left unilateral). The patients' bone age was assessed by means of the Cervical Stage method (CS). The correlation between the bone age and chronological age was defined with the division into male and female patients. RESULTS: The results showed the relationship between the skeletal age and chronological age by gender and cleft type (the differences between the types of clefts by gender were presented). The correlation rate between the values of variables was defined. CONCLUSIONS: The chronological age of children with developmental craniofacial defects (primary and secondary palate cleft) in relation to the stages of skeletal development, indicates a difference of about one year in plus and that fact should be taken into account when choosing orthodontic treatment.

Changes in the masticatory organ in patients with Recklinghausen's disease - a case report.

In the report the authors present changes in the masticatory organ in the case of a 9-year-old girl affected with Recklinghausen's disease. The characteristics included neurofibromatosis of the face, salivary gland and external ear in the form of an extensive tumour. The disease also resulted in acute right hemifacial hypertrophy. The computer-assisted tomography examination identified acute atrophy of the zygomatic bone, maxilla, mandible alveolar ridge and right base of the skull. The clinical intraoral examination of the patient revealed right buccal occlusion and lingual occlusion on the opposite side. The patient underwent functional orthodontic treatment of the co-existing malocclusion with an orthodontic appliance for the upper and lower jaw which was to prevent further mandible movement towards the right. According to researchers, neoplasia is an inherent characteristic of a phenotype seen in patients suffering from Recklinghausen's disease. Therefore, it is the main factor influencing the selection of a therapy. Although there are certain single attempts of pharmacological treatment of ganglioneurofibromas at their early development stage, it is agreed that, in fact, no preventive actions are possible. Hence, in the case of neurofibromatosis type 1, reconstruction and aesthetic procedures are widely applied in treating the disease.

The Evaluation of Facial Muscles by Surface Electromyography in Very Preterm Infants.

BACKGROUND: It is reported that 40% of preterm infants have problems with eating. Neonatal feeding disorders may be one of the factors increasing neonatal mortality. The aim of our study was to evaluate the muscles involved in suckling and swallowing in premature newborns using surface electromyography (sEMG). We would like to objectively describe the tension of muscles engaged in feeding in order to properly plan the therapy. Another aim was to compare sEMG measurements to gestational age, birth weight, and umbilical blood pH to show which parameters put children at risk of feeding problems. METHODS: Sixteen preterm neonates with gestational age less than 32 weeks, birth weight less than 1500 g, and oral feeding difficulties were analyzed for muscle response and electrical activity of nerves using sEMG (surface electromyography). RESULTS: We found a negative correlation indicating that preterm infants with a younger gestational age had higher suprahyoid muscle tension, and a positive correlation was found between pH value and suprahyoid muscles. The lower the pH value, the lower the tension in the suprahyoid muscles. CONCLUSIONS: sEMG may be a helpful diagnostic tool in the evaluation of the masticatory system of premature infants. Due to the abnormal tone of the muscles responsible for swallowing, it is advisable to rehabilitate as early as possible.

The Influence of Parent Education on the Neurobehavior and Sucking Reflexes of Very Preterm Infants.

The diagnosis of neurobehavioral problems in very preterm neonates helps with planning and applying proper and direct therapeutic interventions. (1) Background: The aim of this study was to determine the direct impact of neurobehavior on the sucking reflex and eating abilities of neonates. (2) Methods: We assessed 18 preterm neonates twice hospitalized at the Gynecology and Obstetrics Clinical Hospital through the use of the Neonatal Behavioral Assessment Scale (NBAS). (3) Results: We found that that a neonate's sucking ability positively correlated with the activity level item from the motor system cluster of the NBAS. (4) Conclusions: Neurobehavior should be closely assessed in very preterm neonates. Firstly, because assessments can detect fundamental problems and help a practitioner plan for early intervention. Secondly, the education of parents regarding the neurobehavior of their child can help in the facilitation of feeding skills and the planning of early rehabilitation.

Atelocollagen Application in Human Periodontal Tissue Treatment-A Pilot Study.

BACKGROUND: The aim of this study is the clinical observation of gingival tissue condition after atelocollagen injection. METHODS: In 18 patients, 97 gingival class I Miller recessions were divided according to recession height, gingival papillae loss and thickness of gingivae. Atelocollagen (Linerase, 100 mg) was injected into keratinized gingivae twice or thrice, at two-week intervals. RESULTS: Statistically significant changes in gingival recession, amount of gingival papillae loss and thickness of gingiva were observed, after both two and three collagen injections. Although the degree (height) of recession decreased and gingival tissue thickness increased with every injection; there was no difference in gingival papillae loss between second and third collagen injections. CONCLUSIONS: The injectable form of atelocollagen is a promising material for gingival soft tissue regeneration and stimulation and allows for reduction in the number of procedures and support in a variety of surgical scenarios. This is a pilot study that clinically measures the impact of injected atelocollagen on periodontal tissue biotype, including the thickness of gingivae and gingival papillae regeneration.

Ototoxicity after platinum-based chemotherapy in the treatment of melanotic neuroectodermal tumour of infancy.

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare infantile tumor that originates from mesenchymal-neuroectodermal cells, the treatment of which uses platinum derivatives that can affect hearing loss. The present study evaluated the long-term effects of ototoxicity following chemotherapy with cisplatin, vincristine, cyclophosphamide, teniposide and adriamycin in a 10-year-old patient after surgical removal of a MNTI tumor at the age of 8 months. Audiometric tests (high-frequency tonal audiometry, speech audiometry, speech acoustics, tympanometry and absorbance measurements) were performed during a 10-year follow-up after receiving chemotherapy. Hearing disorders in the high-frequency range (6,000 to 16,000 Hz range) were demonstrated for both ears, indicating that these may be the long-term effects of chemotherapy with use of platinum compounds during the treatment of infants.

Cleidocranial Dysplasia-dental Disorder Treatment and Audiology Diagnosis.

A review of numerous case reports was made, in order to demonstrate the possibilities for treatment of dental disorders in patients with Cleidocranial dysplasia (CCD). In this paper, our own report, including a diagnosis of the effect on the auditory system, is presented. In addition to the triad of CCD symptoms that include hypoplastic or aplastic clavicles, impacted and supernumerary teeth, delayed closure of fontanelles and cranial sutures, impairment of the hearing system resulting in conductive hearing loss also occurs. Our own report is based on the case of a 12-year-old CCD patient, in whom Cone Beam Computed Tomography (CBCT) revealed the presence of 12 supernumerary teeth. Furthermore, a clinical examination pointed to the presence of retained deciduous teeth and a delayed eruption of permanent teeth. Orthodontic-surgical procedures were implemented, in accordance with the literature. During the course of the orthodontic treatment, a decrease in auditory sensitivity was observed, for which reason hearing tests were also performed. Conductive hearing loss was detected. As such, it is important to remember that in such cases, auditory check-ups need to be performed between the many surgical and orthodontic interventions, which usually last a few years.

Electromyographic Analysis of Masticatory Muscles in Cleft Lip and Palate Children with Pain-Related Temporomandibular Disorders.

Aim: The aim of this study was to assess the electrical activity of temporalis and masseter muscles in children with cleft lip and palate (CLP) and pain-related temporomandibular disorders (TMD-P). Methods: The sample consisted of 31 CLP patients with a TMD-P (mean age 9.5 ± 1.8 years) and 32 CLP subjects with no TMD (mean age 9.2 ± 1.7 years). The children were assessed for the presence of temporomandibular disorders (TMD) using Axis I of the Research Diagnostic Criteria for TMD (RDC/TMD). Electromyographical (EMG) recordings were performed using a DAB-Bluetooth Instrument (Zebris Medical GmbH, Germany) in the mandibular rest position and during maximum voluntary contraction (MVC). Results: The rest activity of the temporalis and masseter muscles was significantly higher in TMD-P group compared with non-TMD children. A significant decrease in temporalis muscle activity during MVC was observed in TMD-P patients. There was a significant increase in the Asymmetry Index for temporalis and masseter muscle rest activity in the TMD-P group. Conclusion: Cleft children diagnosed with TMD-P have altered masticatory muscle activity, and this can affect their muscle function.

Electromyographic analysis of superior orbicularis oris muscle function in children surgically treated for unilateral complete cleft lip and palate.

PURPOSE: The aim of this study was to assess the electrical activity of the superior orbicularis oris muscle in children surgically treated for unilateral complete cleft lip and palate (UCCLP). MATERIAL AND METHODS: The sample comprised 45 patients 6.38-12.68 years of age with UCCLP and 40 subjects 6.61-11.71 years of age with no clefts. Electromyographical (EMG) recordings were taken with a DAB-Bluetooth Instrument (Zebris Medical GmbH, Germany) in the rest position and during saliva swallowing, lip protrusion and reciprocal compression of the lips, as well as while producing the phonemes /p/, /b/, and /m/ combined with the vowel /a/. RESULTS: The electrical activity of the upper lip during saliva swallowing and lip compression was significantly greater in the cleft group. Similar resting level activity was observed in both groups. During the production of the /p/, /b/, and /m/ phonemes combined with the vowel /a/ the results showed no significant differences in the EMG activity between children with UCCLP and noncleft subjects. CONCLUSION: Patients with UCCLP have abnormal upper lip function characterized by increased activity of the superior orbicularis oris muscle during saliva swallowing and lip compression, and this may affect facial morphology.

Analysis of skeletal maturity of children with cleft palate in terms of healthy children by the CVM method.

BACKGROUND: For many years, the analysis of bone age X-rays have been used for the hand and wrist, which were assessed on the basis of changes in the various centers of ossification. These images, however, do not constitute a diagnostic element of cleft defects, leading to additional exposure of the patient to X-rays. The problem was solved by using lateral head films, which enabled the interpretation of the morphological changes in the cervical spine to evaluate skeletal development stages. OBJECTIVES: The objective of this work is to define the differences between the skeletal age and chronological age of children with malocclusion and congenital craniofacial disorders - primary and secondary palate cleft. MATERIAL AND METHODS: The study material comprised 90 lateral cephalometric radiographs of patients at the age of 7 to 16 (45 lateral head radiographs of patients with various occlusion disorders and 45 lateral head radiographs of patients with various types of primary and secondary palate cleft). Then, all the lateral cephalometric radiographs were analysed in terms of the shape of the 2nd, 3rd and 4th cervical vertebra in line with the Cervical Stage method (CS), developed by Baccetti et al. in 2005. RESULTS: Patients with malocclusions without malformations achieved various stages of bone development at an earlier chronological age compared with patients with primary and secondary palate. An exception was the phase CS 3 (early growth spurt) development disorders, in which patients with different types of cleft had lower chronological age compared with patients with malocclusion. CONCLUSIONS: The method that allows for an assessment of the development of skeletal maturity is the analysis of the shape of the cervical vertebrae in lateral head film.

Rehabilitation of the orofacial complex by means of a stimulating plate in children with Down syndrome.

BACKGROUND: Disorders in the orofacial complex as well as muscle hypotension in children with Down syndrome can be corrected through orofacial therapy that makes use of a palatal plate. OBJECTIVES: The aim of this paper was to present how parents of children with DS assess the availability of treatment and the therapeutic effects of orthodontic palatal plate therapy on the tongue position and mimetic muscle tension in their children; and to determine whether implementing full Castillo-Morales therapy and using only a palatal plate lead to substantially different results. MATERIAL AND METHODS: The study was conducted on 100 children with DS between the ages of two months and two years (44 boys, 56 girls) who were treated by means of stimulating plate therapy. The study analyzed responses obtained from the parents to questions included in a questionnaire completed at every visit over a period of two years. RESULTS: The study found that in 50 patients with DS who underwent palatal plate rehabilitation there was a visible improvement of the mimetic muscles, tongue retraction and lip closure. CONCLUSIONS: Early orthodontic palatal plate therapy ought to be an integral part of the multidisciplinary rehabilitation of patients with DS.

Characteristics of dental pulp in human upper first premolar teeth based on immunohistochemical and morphometric examinations.

Teeth extracted for orthodontic reasons are commonly considered as healthy. Therefore, it is possible to examine structure of the dental pulp can be fully recognized and how it is affected by malocclusion. The aim of the study was to evaluate by immunohistochemistry (IHC) and morphometry dental pulp in human upper first premolar teeth extracted for orthodontic reasons. The material comprised 36 teeth of 20 patients in the age range 16-26 years. By the use of IHC markers the presence of immunocompetent cells (CD20, CD45RO, and CD68), blood vessels (CD31) and nerves (PGP9.5) were examined in the pulp. Inflammatory infiltrates and tissue atrophy were observed in 24 and 10 teeth, respectively. Strong positive correlation between the width of the odontoblastic layer, the number of rows of odontoblast nuclei and the increase of MVA (microvessel area) in the pulp of atrophic teeth was found. The cellular infiltrations found in H&E-stained sections were identified by IHC as memory T cells (CD45RO+) and B lymphocytes (CD20+) with macrophages (CD68+) present at the periphery. The CD20 antigen was intensively expressed in 13 teeth, CD45RO in 33 teeth, and CD68 in 20 teeth. Thus, despite the lack of any clinical signs of pulp disease many teeth extracted for orthodontic reasons show focal pulp inflammation and atrophy which probably results from the malocclusion stress accompanying teeth crowding.